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LSD impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision making

Thomas Pokorny, Patricia Duerler, Erich Seifritz, Franz X. Vollenweider, Katrin H. Preller

bioRxiv Preprint Server January 28, 2019 preprint DOI: 10.1101/532234 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, randomized, placebo-controlled, within-subject design
Sample size 25
Population Healthy participants
Interventions LSD ketanserin
Dose 100 µg LSD, 40 mg ketanserin
Topics LSD
Citations 2
Key points LSD impaired executive functions, cognitive flexibility, and working memory, but not decision-making or risk-taking, and these impairments were normalized by ketanserin.

Abstract

Psychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied. Therefore, we examined the acute effects of LSD (100µg) alone and in combination with the 5-HT2A antagonist ketanserin (40mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery. Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits. The present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.

Comparable studies

Other randomized controlled trials on LSD, most cited first.

Study Year Design Participants
Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases 2014 Randomized controlled trial n = 12
Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users 1994 Double-blind, saline placebo-controlled, randomized study n = 12
Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) 2014 Double-blind, randomized, placebo-controlled, crossover study n = 16
Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants 2018 Double-blind, randomized, counterbalanced, cross-over study n = 24
LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults 2016 Balanced-order, placebo-controlled study n = 19

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